Star block-copolymers: Enzyme-inspired catalysts for oxidation of alcohols in water

Article abstract of DOI:10.1039/c4cc03370a

A number of fluorous amphiphilic star block-copolymers containing a tris(benzyltriazolylmethyl)amine motif have been prepared. These polymers assembled into well-defined nanostructures in water, and their mode of assembly could be controlled by changing the composition of the polymer. The polymers were used for enzyme-inspired catalysis of alcohol oxidation. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc03370a

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Star block-copolymers: enzyme-inspired catalysts
for oxidation of alcohols in water†
Cite this: Chem. Commun., 2014,
50, 7862
Clement Mugemana, Ba-Tian Chen, Konstantin V. Bukhryakov and
´
Valentin Rodionov*
Received 6th May 2014,
Accepted 23rd May 2014
DOI: 10.1039/c4cc03370a
www.rsc.org/chemcomm
A number of fluorous amphiphilic star block-copolymers containing Sheldon,7 Stahl8 and others,9 has emerged as one of the most
a tris(benzyltriazolylmethyl)amine motif have been prepared. These attractive catalysts for selective aerobic oxidation of primary
polymers assembled into well-defined nanostructures in water, alcohols.10 The established protocols for Cu/TEMPO catalyzed alcohol
and their mode of assembly could be controlled by changing the oxidation strongly favor organic solvents, especially acetonitrile.8 We
composition of the polymer. The polymers were used for enzyme- aimed to design an enzyme-inspired functional macromolecular
inspired catalysis of alcohol oxidation.
architecture that could enable the transfer of this catalytic system
to pure water. Such a transfer could enable large-scale applications of
Nature’s enzymes are complex polymer catalysts that are capable Cu/TEMPO, while circumventing the usual safety concerns associated
of facilitating thousands of challenging reactions with perfect with combining oxygen and organic solvents.
fidelity and selectivity. This exquisite level of functionality is
We envisioned that amphipolar, globular assemblies, with
achieved through precise, programmed folding into intricate metal-binding sites buried inside hydrophobic cores (Fig. 1a),
tertiary structures1 and close participation of cofactors, prosthetic could provide the necessary site isolation of the catalytic metal
groups and metal ions. Often, the active sites and cofactor binding centers.11 However, the accumulation of hydrophobic reaction
pockets are separated from the bulk aqueous phase and buried in products inside such assemblies would be undesirable, as the
the hydrophobic interior of the protein.
transfer of an additional alcohol substrate to the active site
Recent publications explored the use of chemist-made macro- would be hindered. To avoid this potential problem, we chose
molecules, either branched2,3 or single-chain,4 as enzyme-inspired ‘‘everything-phobic’’ fluorous monomers as building blocks for
catalysts. Rational design of linear polymers with protein-like the cores of our prospective catalysts.12,13 Understanding that
tertiary or quaternary structures and catalytic function remains perfluorocarbons and their emulsions in water are capable of
an elusive (but tantalizing) goal.5 Materials with branched topolo- dissolving substantial amounts of O2,14,15 we reasoned that a
gies are amenable to structural engineering, at the cost of greater fluorous core of a polymer globule could pre-concentrate
synthetic complexity (dendrimers) or increased heterogeneity (star oxygen in the vicinity of the active metal site.
polymers).
We selected the tris(benzyltriazolylmethyl) amine (TBTA)
In this study, we present a pathway to enzyme-inspired catalytic motif16 as a metal-binding site, due to its ability to stabilize
materials based on star block-copolymers with limited branching. the CuI oxidation state, its versatile coordination chemistry17
These polymers incorporate hydrophilic, superhydrophobic, and (Fig. 1b), and its easy synthetic accessibility. Starting with the
polydentate metal-binding characteristics. The interplay of these TBTA-based polymerization initiator 1 (Fig. 1c), we proceeded
structural characteristics determines the mode of self-assembly to synthesize a number of superhydrophobic three-arm poly-
and the catalytic competence of the macromolecules.
mers via nitroxide-mediated polymerization (NMP).18 We chose
The Cu/TEMPO (2,2,6,6-tetramethyl-1-piperidine-N-oxyl) system, this mode of polymerization over synthetically simpler atom-
introduced by Semmelhack6 in 1984 and further developed by transfer radical polymerization,19 as the latter can be affected
by the presence of CuI binding sites in the target polymers.
KAUST Catalysis Center and Division of Physical Sciences and Engineering,
King Abdullah University of Science and Technology, Thuwal, 23955-6900,
Kingdom of Saudi Arabia. E-mail: valentin.rodionov@kaust.edu.sa;
Tel: +966 (12) 8084592
Pentafluorostyrene (PFS), 2,2,3,3,4,4,4-heptafluorobutyl acrylate
(PFBA) and 1H,1H,2H,2H-perfluorodecyl acrylate (PFDA) were poly-
merized with initiator 1, either in the bulk or in cyclohexanone at
120 1C. For each fluorinated monomer, we aimed to create at least
two macroinitiators with different degrees of polymerization (DP)
to evaluate the effects of the hydrophobic core size on catalytic
† Electronic supplementary information (ESI) available: Experimental details for
polymer and organic synthesis; characterization (1H, 13C, and 19F NMR, FTIR
spectra). See DOI: 10.1039/c4cc03370a
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Fig. 1 (a) Design for an amphiphilic block copolymer micelle with metal binding sites at the core. (b) Some of the modes of coordination possible for a
TBTA-type ligand. (c) Synthesis of amphiphilic star block copolymers.
competency (Table S3, ESI†). A DP higher than 4 could not be (PFBA7-b-OEGMa18)3, (PFBA14-b-OEGMa30)3, (PFDA4-b-OEGMa30)3,
reached for PFDA due to the anomalously low solubility of resulting and (PFS16-b-OEGMA30)3 (Fig. 2a–c, and Sections 4.6–7, ESI†). AFM
polymers.
phase images (Fig. 2b and Section 4.6, ESI†) revealed the separation
The hydrophobic macroinitiators were used for the polymer- between the hydrophobic aggregate cores and hydrophilic coronas.
ization of two hydrophilic monomers, p-oligo(ethylene glycol) The size of the aggregates observed was consistent between cryo-
styrene (OEGSt) and oligo(ethylene glycol) methacrylate (OEGMA). TEM and AFM, taking into account the flattening/spreading of the
OEGSt was polymerized in cyclohexanone, leading to a range of soft material on the substrate (Table 1 and Table S2, ESI†).
amphiphilic star copolymers (Table 1, entries 1–5). Although
We found that by increasing the weight fraction of the
NMP is rarely a polymerization of choice for methacrylates,20 we fluorinated block in the copolymer, more complex morpholo-
obtained a higher DP for the copolymerization of OEGMA than gies could be triggered. The (PFBA20-b-OEGSt4)3 copolymer,
we did for styrenic OEGSt (Table 1, entries 6–9). Size exclusion which contains 67 wt% of the fluorous monomer, assembled
chromatography (SEC) on all the copolymerization reactions into well-defined vesicles, unilamellar (Fig. 2f), as well as
indicated a clean shift of population towards a higher number- multilamellar (Fig. 2g). The thickness of the vesicle boundaries
average molecular weight (Mn), with little to no tailing (although was ca. 9 nm, which suggests that they were formed by a single
limited aggregation was observed for (PFDA4-b-OEGSt4)3 and layer of macromolecules. The AFM image of (PFBA20-b-OEGSt4)3
(PFBA20-b-OEGSt4)3).
showed that some vesicles remain intact even in the partially
We investigated the self-assembly modes of the copolymers by dry state. Objects with diameters ranging from ca. 60 to 120 nm
obtaining cryogenic transmission electron microscopy (cryo-TEM) and with heights from 30 to 40 nm were observed. In addition
and atomic force microscopy (AFM) images of their aggregates. to the aggregates with pronounced height, flat structures of
Spherical aggregates with diameters between 20 and 50 nm were the similar lateral dimensions could be seen (Fig. 2d–e). We pre-
main type of assemblies for (PFS7-b-OEGSt3)3, (PFS10-b-OEGSt4)3, sume that some of the vesicles retain their interior water when
Table 1 Characterization of amphiphilic star block copolymers
Polymera
Mn
Mw
PDISEC
DLSc (nm)
PDIDLS
AFMd (nm)
TEM (nm)
b
b
Entry
1
2
3
4
5
6
7
8
9
(PFS7-b-OEGSt3)3
(PFS10-b-OEGSt4)3
(PFS16-b-OEGSt4)3
(PFBA20-b-OEGSt4)3
(PFDA4-b-OEGSt4)3
5900
11 200
12 400
12 800
11 500
13 500
11 230
13 200
11 000
6600
13 216
15 130
16 400
14 720
16 470
13 360
15 970
12 320
1.12
1.18
1.22
1.28
1.28
1.22
1.19
1.21
1.12
20(90%)/160(10%)
28(30%)/135(70%)
70(70%)/130(30%)
70
20(90%)/140(10%)
120(42%)/200(58%)
30(48%)/300(52%)
30(89%)/250(11%)
40(86%)/255(14%)
0.23
0.22
0.24
0.36
0.54
0.22
0.28
0.29
0.44
76 Æ 10
44 Æ 6
46 Æ 4
100 Æ 14
74 Æ 4
70 Æ 6
70 Æ 8
88 Æ 4
76 Æ 10
20 Æ 2 f
26 Æ 2 f
42 Æ 4e
120–350 f
22 Æ 1 f
44 Æ 8 f
58 Æ 10e
52 Æ 10e
24 Æ 4 f
(PFS16-b-OEGMA30 3
(PFBA7-b-OEGMA18 3
(PFBA14-b-OEGMA30 3
(PFDA4-b-OEGMA30 3
)
)
)
)
a
b
c
Degree of polymerization determined by 1H NMR. Determined by SEC (calibration against linear polystyrene). Hydrodynamic diameters
determined by dynamic light scattering (DLS) in water at 1 g LÀ1. For multimodal distributions, diameters are estimated based on intensity
distribution, and relative ratios based on volume distribution. Diameters of aggregates determined from AFM height images. Diameter of
aggregates determined from TEM images. Diameter of aggregates determined from cryo-TEM images.
d
e
f
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amount of Cu was sequestered in the vesicle’s boundary, as
evidenced by the increased contrast in the cryo-TEM image
(Fig. 2h).
Examination of aqueous polymer solutions by DLS (Section
4.5, ESI†) revealed 20–70 nm aggregates in agreement with AFM
and TEM images, as well as larger species with hydrodynamic
diameters varying from ca. 100 to 300 nm. It is likely that the
larger species are not abundant enough to feature prominently
in TEM images, and unravel/disassemble when spread on AFM
substrates. Much smaller, 5–20 nm species were observed in
the polymer solutions prepared in good organic solvents, such
as DMF and THF (Fig. S41–S42, ESI†).
The catalytic competency of the star polymers was evaluated
for a Cu/TEMPO-catalyzed alcohol oxidation reaction, using a
modification of the protocol originally reported by Stahl.8
Polymers were dispersed in water, the ‘‘cofactors’’ TEMPO
and 4-dimethylaminopyridine (DMAP) were added, and the
solutions were treated with ultrasound. CuSO4 and benzyl
alcohol were added to start the reaction. The rate of oxidation
was negligible in the absence of the star polymers (Table 2,
entries 1 and 2). Addition of PFS and PFDA copolymers led to a
marginal improvement of reaction yields (Table 2, entries 3,
5 and 7). To our delight, the TEMPO–Cu system became
catalytically competent in the presence of star polymers with
PFBA hydrophobic cores (Table 2, entries 4, 6 and 8). The
nature of the hydrophilic monomer, the degree of polymeriza-
tion, or the weight fraction of the fluorinated monomer had little
influence on the catalytic competency: (PFBA20-b-OEGSt4)3,
(PFBA7-b-OEGMA18)3, and (PFBA14-b-OEGMA30)3 were similar in
their capacity for catalyzing alcohol oxidation. Upon further
optimization of reaction conditions (Table 2, entries 9–12), an
almost quantitative yield of benzaldehyde was obtained in the
presence of (PFBA14-b-OEGMA30)3.
Fig. 2 (a) and (b) AFM height and phase images of (PFS16-b-OEGMA30 3
block copolymer micelles spin-coated onto a Si substrate. (c) Cryo-TEM
)
image of (PFS16-b-OEGMA30)3 block copolymer micelles in water. (d) and
(e) AFM height and phase images of (PFBA20-b-OEGSt4)3 vesicular struc-
tures. (f) and (g) Cryo-TEM images of (PFBA20-b-OEGSt4)3 vesicular
structures, unilamellar and multilamellar. (h) Cryo-TEM image of
a
(PFBA20-b-OEGSt4)3 vesicle in the presence of CuSO4.
The capacity of the polymers to pre-concentrate molecular
oxygen was assessed next. Polymer solutions (2 wt%) were
saturated with O2 by vigorous shaking in vials in an atmosphere
of pure oxygen. Following this, the vial headspace was vented,
and the concentration of O2 in solution was measured in 5 min
deposited on the substrate, while others ‘‘deflate’’ and spread.
Unlike spherical aggregates, the ‘‘deflated’’ vesicles show no
core–corona contrast in the AFM phase image. The vesicular
structures persisted after addition of CuSO4. A significant
Table 2 Catalytic oxidation of benzyl alcohol in the presence of block-copolymer micellar aggregates
TEMPOa [mol%]
DMAPa [mol%]
CuSO4 [mol%]
Polymer [wt%]
Conversionb [%]
a
Entry
Block copolymer
Time [h]
1
2
3
4
5
6
7
8
—
—
36
44
36
36
36
36
36
36
37
31
21
44
1
2.5
1
1
1
1
1
1
5
50
5
5
5
5
5
5
25
25
25
50
0.2
2
—
—
o1
5
6
28
5
25
6
22
46
53
61
90
(PFS10-b-OEGSt4)3
(PFBA20-b-OEGSt4)3
0.2
0.2
0.2
0.2
0.2
0.2
4
2
2
2
0.04
0.04
0.04
0.04
0.04
0.04
3.11
1.56
1.27
1.56
(PFS16-b-OEMa30 3
(PFBA7-b-OEGMa18 3
(PFDA4-b-OEGMa30 3
(PFBA14-b-OEGMa30 3
(PFBA14-b-OEGMA30 3
(PFBA14-b-OEGMA30 3
(PFBA14-b-OEGMA30 3
(PFBA14-b-OEGMA30 3
)
)
)
)
)
)
)
9
2.5
2.5
5
10
11
12
)
2.5
a
b
Relative to benzyl alcohol. Determined by 1H NMR.
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3 M. Zhao, B. Helms, E. Slonkina, S. Friedle, D. Lee, J. DuBois,
intervals using an Inlab 605 probe (Mettler Toledo). For both pure
water and (PFS16-b-OEGSt4)3 solution, the dissolved O2 concen-
tration dropped to its air-saturated value of B9 mg LÀ1 in
B25 min (Fig. S69, ESI†). Similar equilibration kinetics was
observed for the 2 wt% solution of Pluronic P123. Since Pluronic
solutions are prone to foaming, the slightly slower O2 release in
this case compared to pure water can be attributed to gas retention
in foam bubbles. The behavior of the (PFBA14-b-OEGMA30)3
solution was markedly different. After 30 min, the dissolved O2
concentration was still B20 mg LÀ1, which is approximately 200%
of air-saturated concentration in pure water. This suggests that the
catalytic competency of amphiphilic PFBA copolymers is due to
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In conclusion, we prepared a library of well-defined star
block-copolymers from a trifunctional nitroxide initiator based
on the TBTA motif. In water, the copolymers self-assemble into
micelles or vesicles, depending on the specific polymer compo-
sition. Copolymers containing PFBA monomers show evidence
of molecular oxygen pre-concentration in the fluorinated cores
of their micellar aggregates. In combination with DMAP and
TEMPO ‘‘cofactors’’ and in the presence of CuSO4, these
copolymers act as competent catalysts for oxidation of alcohols
to aldehydes in water.
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Authors are grateful to Prof. Nikos Hadjichristidis for help-
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‘‘Catalysis with Soft Materials’’) is acknowledged with thanks.
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